PROJECT SUMMARY This proposal is submitted in response to the NIH Exploratory Bioengineering Research grants program. The proposal develops a technology platform that will enable the parallel measurement of intracellular dynamics from ensembles of neurons in cortical circuits in awake, behaving rodents in a fully automated fashion. We will develop a novel, high-density, multichannel whole-cell patch-clamping platform that is guided by recently developed algorithms that enable automated intracellular recordings in vivo. The three Specific Aims provide for a systematic development of the proposed technologies and application to an urgent systems neuroscience question. AIM 1 develops the surgical methodology, electrode localization strategies and custom skeletal implants for to distribute robotic patch clamping electrodes to the requisite targets in the cortex. AIM 2 develops the parallel patch-clamp robot itself as well as the algorithms to control dense arrays of intracellular recording electrodes. AIM 3 will utilize the functionally characterized platform to obtain parallel whole-cell patch-clamp recordings in behaving mice within and across different lamina and circuits in a cortical association area. This project is well suited to the goals of bioengineering research program ? we are using a multidisciplinary approach to develop a robotic platform that removes a critical barrier for studying neuronal circuit functioning with a high degree of cell and circuit specificity during behavior. The successful development of this technology platform will empower neuroscientists to map the activities of neurons in specific circuits throughout the nervous system, enabling a mechanistic understanding of how circuits function in behaviors, and reveal how cells and circuits go awry in pathological states.